Physiological and pharmacological studies suggest that neuropeptides may modulate the activity of specific neuronal systems in brain, particularly monoaminergic and sensory neurons. However, for most of the neuropeptides such as enkephalin, substance P and angiotensin II, detailed anatomical studies of the development, fiber connections, and synaptic relations with neurons containing more conventional neurotransitters are not available. In the proposed studies, light and electron microscopic immunocytochemistry will be used to examine the ontogeny of neurons containing these three neuropeptides in the fetal rat brain and to examine the anatomical relations between the neuropeptide-containing neurons and monoaminergic and/or sensory afferents in the nucleus tractus solitarius, a primary visceral afferent termination and in the nucleus caudalis of the spinal trigeminal, a primary somatic afferent termination in adult rat brain. In order to investigate the synaptic relations of monoaminergic and peptidergic neurons in the respective brain regions of adult rats, the immunocytochemical localization of the neuropeptides will be combined with immunocytochemical localization of the monoamine synthesizing enzymes, or the radioautographic localization of 3H-norepinephrine or 3H-serotonin. The information to be gained from these studies should provide an anatomical substrate for understanding how these peptides acting individually or in combination with each other or with specific monoaminergic neurons can elicit analgesic, cardiovascular and other physiological changes at least partially controlled by neuropeptides in the central nervous system (CNS).